chr1-172551525-C-T

Variant names:

• chr1-172551525-C-T
• rs201186467
• NM_014283.5:c.76C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014283.5(SUCO):​c.76C>T​(p.Arg26Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,603,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R26H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: SUCO NM_014283.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.24
• Publications: 3 publications found

Genes affected

SUCO (HGNC:1240): (SUN domain containing ossification factor) Predicted to be involved in positive regulation of collagen biosynthetic process; positive regulation of osteoblast differentiation; and regulation of bone remodeling. Predicted to be located in rough endoplasmic reticulum. Predicted to be active in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUCO Gene-Disease associations (from GenCC):

• osteogenesis imperfecta

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• temporal lobe epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1786493).
• BS2: High AC in GnomAd4 at 21 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014283.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	NM_014283.5	MANE Select	c.76C>T	p.Arg26Cys	missense	Exon 2 of 24	NP_055098.1	Q9UBS9-1
	SUCO	NM_016227.4		c.661C>T	p.Arg221Cys	missense	Exon 3 of 23	NP_057311.3	Q9UBS9-2
	SUCO	NM_001282750.2		c.76C>T	p.Arg26Cys	missense	Exon 2 of 23	NP_001269679.1	B4DYM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCO	ENST00000263688.4	TSL:1 MANE Select	c.76C>T	p.Arg26Cys	missense	Exon 2 of 24	ENSP00000263688.3	Q9UBS9-1
	SUCO	ENST00000367723.8	TSL:1	c.661C>T	p.Arg221Cys	missense	Exon 3 of 23	ENSP00000356696.4	Q9UBS9-2
	SUCO	ENST00000616058.4	TSL:1	c.-1454C>T		5_prime_UTR	Exon 2 of 22	ENSP00000479061.1	A0A087WV04

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 151842 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000949 AC: 23 AN: 242348 AF XY: 0.0000914

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000922

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000138 AC: 200 AN: 1451418 Hom.: 0 Cov.: 29 AF XY: 0.000134 AC XY: 97 AN XY: 721958

African (AFR) AF: 0.000122 AC: 4 AN: 32860

American (AMR) AF: 0.000115 AC: 5 AN: 43468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.00 AC: 0 AN: 39004

South Asian (SAS) AF: 0.0000354 AC: 3 AN: 84746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000167 AC: 185 AN: 1106584

Other (OTH) AF: 0.0000501 AC: 3 AN: 59884

GnomAD4 genome AF: 0.000138 AC: 21 AN: 151842 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74156

African (AFR) AF: 0.0000967 AC: 4 AN: 41354

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67900

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000198 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.023	D
Polyphen		0.83	P
Vest4		0.50
MVP		0.22
MPC		0.47
ClinPred		0.11	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.16
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201186467; hg19: chr1-172520665;